基于中性粒细胞胞外诱捕网调控钙黏蛋白5改善心肌梗死的机制及暖心康入组织成分研究OA

Objective:To investigate the mechanism by which Nuanxinkang(NXK)improves cardiac function following myocardial infarction(MI)by intervening in the formation of neutrophil extracellular traps(NETs),thereby alleviating inflammatory damage to cadherin 5(CDH5)-a key junctional protein in cardiovascular endothelium-and to identify the chemical composition of NXK and its components that penetrate heart tissue.Methods:Eighty male C57BL/6J mice were randomly assigned into four groups(n=20):Sham,Model(MI),NXK,and NETs inhibitor(Apocynin).The groups received their respective treatments for 1 or 8 weeks.Left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)were assessed via echocardiography.Hematoxylin-eosin(HE)and sirius red staining were employed to evaluate cardiac microvascular structure,inflammatory infiltration,and fibrosis.Immunofluorescence staining was used to observe the expression of myeloperoxidase(MPO)and CDH5 in cardiac microvessels.Peripheral blood levels of N-terminal pro-B-type natriuretic peptide(NT-proBNP)were measured by ELISA.High-resolution mass spectrometry(HRMS)was performed to analyze the chemical constituents of the NXK formula and its components localized within heart tissue.Results:Compared with the MI group,both the NXK and Apocynin groups exhibited significantly improved endothelial cell morphology,reduced inflammatory cell infiltration,and attenuated fibrosis.Both treatments led to enhanced cardiac function,characterized by increased LVEF and LVFS values(P＜0.01,P＜0.05)and decreased NT-proBNP levels(P＜0.05,P＜0.01).NXK significantly reduced the expression of MPO in cardiac microvessels(P＜0.01)while upregulating the expression of CDH5(P＜0.01).Mass spectrometry identified a total of 3180 compounds in the NXK formula,with 451 components detected in heart tissue.Among these tissue-penetrating components,identified compounds derived from Radix Ginseng Rubra included Ginsenoside Re,Rg2,Rd,Rb2,Chikusetsusaponin V,and 2,2'-methylenebis(4-ethyl-6-tert-butylphenol);asiatic acid was identified as a derivative of Ilex pubescens.Conclusion:Nuanxinkang inhibits the deposition of NETs in coronary microvessels,thereby reducing the inflammatory degradation of CDH5,repairing vascular endothelial cells,reducing infarct size,and improving cardiac function.HRMS identified 451 tissue-penetrating components of NXK,including nine key active ingredients derived from Ginseng and Ilex pubescens.